4,2′,5′-Trihydroxy-4′-methoxychalcone from Dalbergia odorifera exhibits anti-inflammatory properties by inducing heme oxygenase-1 in murine macrophages

• TMC was isolated from Dalbergia odorifera.
• TMC suppressed LPS-induced expression of pro-inflammatory enzymes.
• TMC suppressed LPS-induced production of pro-inflammatory cytokines.
• TMC showed potent the anti-inflammatory effects through Nrf2 pathway-dependent expression of HO-1.
• TMC might have potent therapeutic effects of various inflammatory diseases.

Dalbergia odorifera T. Chen (Leguminosae) has traditionally been used as an ingredient in East Asian medicines to treat various diseases. In the present study, 4,2′,5′-trihydroxy-4′-methoxychalcone (TMC), a biologically active chalcone isolated from the heartwood of D. odorifera, inhibited cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, leading to a reduction in COX-2-induced prostaglandin E2 (PGE2) and iNOS-induced nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages. Furthermore, TMC suppressed tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) production, and the phosphorylation and degradation of IκB-α as well as the LPS-stimulated nuclear translocation of p65 in macrophages. The present study also demonstrated that TMC induced heme oxygenase-1 (HO-1) expression through the nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) in macrophages. The effects of TMC on LPS-induced NO, PGE2, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β production were partially reversed by the HO inhibitor tin protoporphyrin (SnPP). These results suggest that TMC inhibits pro-inflammatory mediators by inducing the expression of anti-inflammatory HO-1 via the Nrf2 pathway.